Synopsis

Source of validity: Scientific
Rating (out of 5): 3

L-5-methyltetrahydrofolate glucosamine salt (5-MTHF) is a biologically active form of folate that plays a crucial role in one-carbon metabolism, including DNA synthesis, repair, and methylation—processes essential for reproductive health. The use of 5-MTHF in supporting or treating infertility is scientifically justified, particularly in individuals with genetic polymorphisms (such as MTHFR C677T) that reduce the conversion of synthetic folic acid to active folate forms. Several studies have shown that adequate folate status is vital for oocyte quality and maturation, implantation, and early embryonic development. Furthermore, folate deficiency and impaired folate metabolism are associated with a higher risk of neural tube defects and infertility in both men and women.

Clinical trials and observational studies suggest that supplementation with 5-MTHF may be superior to folic acid in raising plasma and red blood cell folate concentrations, particularly in those with MTHFR mutations. Some studies have reported improved pregnancy rates in women undergoing assisted reproductive techniques when using active folate forms. In men, folate supplementation may improve sperm quality and count, although evidence is not as robust as in female infertility. Guidelines often recommend folate supplementation for women trying to conceive, and 5-MTHF is increasingly considered for those who do not tolerate or metabolize folic acid efficiently.

Overall, while there is strong biological plausibility and supportive clinical data, large-scale randomized controlled trials specifically assessing fertility outcomes with 5-MTHF are limited, warranting a moderate evidence rating.

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